Expiration date: 06/2025

Description of dosage form:

Tablets 5 mg + 5 mg: oblong, biconvex, white, engraved "5 / 5" on one side and the company's logo ; — on the other.

Tablets 5 mg + 10 mg: square, biconvex, white, engraved "5 / 10" on one side and the company's logo ; — on the other.

Tablets 10 mg + 10 mg: round, biconvex, white, engraved "10 / 10" on one side and the company's logo ; — on the other.

Tablets 10 mg + 5 mg: triangular, biconvex, white, engraved "10 / 5" on one side and the company's logo ; — on the other.

Pharmacokinetics:

The amount of absorption of perindopril and amlodipine in the drug Prestans not significantly different from that in the use of monotherapies.

Perindopril

When ingestion perindopril rapidly absorbed, Cmax in blood plasma is achieved within 1 h. T1/2 of the blood plasma is 1 h.

Perindopril has no pharmacological activity. Approximately 27% of the total number of perindopril taken orally gets into the bloodstream in the form of the active metabolite perindoprilat. In addition to perindoprilat formed another 5 metabolites that do not have pharmacological activity. Cmax perindoprilat in plasma is achieved after 3-4 hours after taking perindopril inside. Eating slows the conversion of perindopril to perindoprilat, thus affecting the bioavailability. Therefore, the drug should be taken 1 time a day, in the morning, before eating.

There is a linear dependence of the concentration of perindopril in blood plasma from its dose. Vd free perindoprilat is approximately 0, 2 l/kg. Relationship of perindoprilat from plasma proteins, primarily with APF, is about 20% and is dose dependent in nature.

Perindoprilat is excreted from the body by the kidneys. The final T1 / 2 of the free fraction is about 17 h, so the equilibrium state is reached within 4 days.

Excretion of perindoprilat slowed in the elderly, as well as in patients with heart and kidney failure (see "Method of application and dose"). Therefore, in these groups of patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

Dialysis clearance of perindoprilat is 70 ml/min.

Pharmacokinetics of perindopril altered in patients with cirrhosis of the liver: the hepatic clearance is decreased in 2 times. However, the number of perindoprilat formed is not reduced, therefore no dose adjustment is required (see "Method of application and dosage" and "Special instructions").

Amlodipine

Cmax of amlodipine in plasma is reached after 6-12 h after administration of the drug inside. The absolute bioavailability is 64-80%, Vd is approximately 21 l/kg. Ingestion not affect the bioavailability of amlodipine. In in vitro studies, it was shown that about 97, 5% of circulating amlodipine is associated with plasma proteins.

The final T1 / 2 amlodipine from blood plasma is 35-50 h, which allows you to take the drug 1 time per day. Amlodipine is metabolized in the liver to form inactive metabolites. About 60% of the dose of amlodipine is excreted in the kidneys, 10% - unchanged.

The time from taking the drug to reach Cmax amlodipine does not differ in elderly and younger patients. In elderly patients, there is a slowdown in the clearance of amlodipine, which leads to an increase in AUC. Elderly patients do not require dose adjustment, but increase the dose of amlodipine should be with caution.

Use in patients with renal insufficiency (see "dosage And administration").

In patients with hepatic insufficiency T1/2 amlodipine increases.

Description of pharmacological action:

Perindopril

Perindopril - inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE inhibitor). ACE, or kininase II, is an exopeptidase that performs both the conversion of angiotensin I into a vasoconstrictor angiotensin II, and the destruction of bradykinin, having a vasodilator effect, to an inactive heptapeptide.

Since ACE inactivates bradykinin, ACE inhibition is accompanied by increased activity of both circulating and tissue kallikrein-kinin system, while also activating the PG system.

Perindopril has a therapeutic effect due to the active metabolite, perindoprilat. Other metabolites have no inhibitory effect on ACE in vitro.

Arterial hypertension. Perindopril is a drug for the treatment of hypertension of any severity. Against the background of its use, there is a decrease in both the garden and the dad in the lying and standing position.

Perindopril reduces peripheral vascular resistance, which leads to a decrease in high blood pressure and improve peripheral blood flow without changing HR.

As a rule, the reception of perindopril increases renal blood flow, the speed of glomerular filtration does not change.

The antihypertensive effect of the drug reaches a maximum of 4-6 hours after a single oral administration and persists for 24 hours.

Antihypertensive effect after 24 h after a single oral administration is about 87-100% of the maximum antihypertensive effect.

Reducing blood PRESSURE is achieved quickly enough.

The therapeutic effect occurs less than 1 month from the start of therapy and is not accompanied by tachycardia. Discontinuation of treatment does not cause withdrawal syndrome.

Perindopril has a vasodilator effect, helps to restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and reduces left ventricular hypertrophy.

Stable coronary artery disease. The efficacy of perindopril in patients with stable coronary artery disease without clinical symptoms of chronic heart failure (12218 patients aged over 18 years) were studied during a 4-year study (EUROPA). 90% of the study participants had previously suffered acute myocardial infarction or coronary revascularization.

Treatment with perindopril tretbutylamine at a dose of 8 mg / day (equivalent to 10 mg perindopril arginine) led to a significant reduction in the absolute risk of complications by 1, 9%, in patients who had previously suffered myocardial infarction or coronary revascularization, the reduction of the absolute risk was 2, 2% compared with the placebo group.

Amlodipine

Amlodipine — CCB-derived digidropiridinovmi series. Amlodipine inhibits the transmembrane transition of calcium ions into cardiomyocytes and smooth muscle cells of the vascular wall.

The antihypertensive effect of amlodipine is due to the direct effect on the smooth muscle cells of the vascular wall. It was found that amlodipine:

• causes dilation of peripheral arterioles, reducing peripheral vascular resistance (afterload) as the heart rate does not change, and the need of myocardium in oxygen
  
• causes expansion of coronary arteries and arterioles in both ischemic and intact areas. In patients with prinzmetals angina it improves coronary blood flow.
  

In patients with hypertension receiving amlodipine 1 times per day provides a clinically significant decrease in blood pressure when standing and lying during the 24 h Antihypertensive effect develops slowly, therefore the development of acute hypotension is unusual.

In patients with angina pectoris taking amlodipine 1 once a day increases exercise tolerance, delays the onset of angina attack and ischemic depression of the ST segment, and also reduces the frequency of angina attacks and the consumption of nitroglycerin (short-acting forms).

Amlodipine has no effect on the lipid profile and does not cause changes in blood plasma hypolipidemic parameters. The drug can be used in patients with concomitant asthma, diabetes and gout.

The efficacy and safety of the use of amlodipine in a dose of 2, 5-10 mg/day or the ACE inhibitor lisinopril in a dose of 10-40 mg/day or thiazide diuretic of chlortalidone at a dose of 12, 5-25 mg/day as first-line drug was studied in 5-year study ALLHAT (33357 patients aged 55 years and older) patients with mild or moderate arterial hypertension, at least one of the additional risk factors of coronary complications such as myocardial infarction or stroke, transferred more than 6 months before inclusion in the study, or other confirmed cardiovascular disease of atherosclerotic origin diabetes cholesterol levels of HDL less than 35 mg/DL left ventricular hypertrophy according to ECG or echocardiography Smoking.

The main criterion for evaluating the effectiveness is a combined indicator of the frequency of deaths from coronary heart disease and the frequency of nonfatal myocardial infarction. No significant differences between the groups of amlodipine and chlortalidone according to the main evaluation criterion were revealed. The incidence of heart failure in the amlodipine group was significantly higher than in the group of chlorthalidone — 10, 2 and 7, 7%, respectively, the overall mortality rate in the group of amlodipine and chlorthalidone did not differ significantly.

Perindopril, amlodipine

Efficacy with long-term use of amlodipine in combination with perindopril and atenolol in combination with bendroflumethiazide in patients aged 40 to 79 years with hypertension and at least 3 additional risk factors: left ventricular hypertrophy according to ECG or echocardiography diabetes mellitus type 2 atherosclerosis of peripheral arteries earlier history of stroke or transient ischemic attack, male sex, age 55 years or older, microalbuminuria or proteinuria, Smoking, ratio of total cholesterol/HDL cholesterol &ge6 early development of CHD in close relatives was investigated in a study ASCOT-BPLA.

The main criterion for evaluating the effectiveness is a combined indicator of the frequency of nonfatal myocardial infarction (including pain-free) and fatal coronary heart disease.

The frequency of complications, provided the main evaluation criterion in the group of amlodipine/perindopril was 10% lower than in the group of atenolol/bendroflumethiazide, but this difference was not statistically significant. In the group of amlodipine/perindopril, there was a significant decrease in the frequency of complications provided for by additional criteria for efficacy (except fatal and nonfatal heart failure).

Indications:

Hypertension and/or coronary artery disease: stable angina in patients who require therapy with perindopril and amlodipine.

Contraindications:

Perindopril

• hypersensitivity to perindopril or other ACE inhibitors
  
• angioedema (angioedema Quincke) in history (including against the background of other ACE inhibitors)
  
• hereditary / idiopathic angioedema
  
• the age of 18 years (efficacy and safety not established).
  

Amlodipine

• hypersensitivity to amlodipine or other dihydropyridine derivatives
  
• expressed arterial gipotenzia (sad less than 90 mm Hg.V.)
  
• obstruction of the output tract of the left ventricle (e.g. severe aortic stenosis)
  
• unstable angina (except prinzmetals angina)
  
• the age of 18 years (efficacy and safety not established).
  

Prestance

• hypersensitivity to the auxiliary substances included in the preparation
  
• renal failure (creatinine Cl <60 ml / min)
  
• the age of 18 years (efficacy and safety have not been established)
  
• hereditary lactose intolerance, lactase deficiency and glucose-galactose malabsorption.
  

Caution: renal artery stenosis (including bilateral), the only functioning kidney, liver failure, renal failure, systemic diseases of connective tissue (incl. systemic lupus erythematosus, scleroderma), therapy immunosuppressants, allopurinol, procainamide (risk of neutropenia, agranulocytosis), reduced BCC (reception dioretikov, salt-free diet, vomiting, diarrhea), atherosclerosis, cerebrovascular disease, renovascular hypertension, diabetes mellitus, chronic heart failure, the use of dantrolene, estramustine, potassium-sparing diuretics, potassium supplements, potassium-containing substitutes salt of food and drugs lithium, hyperkalemia, surgery/General anesthesia, older age, hemodialysis using high-flow membranes (eg AN69), desensitizing therapy, LDL apheresis, aortic stenosis/mitral stenosis/hypertrophic cardiomyopathy, patients of Negroid race.

Use during pregnancy and breast-feeding:

Pregnancy

The drug is contraindicated in pregnancy.

With the exception of cases when the therapy with Prestans necessary for health reasons, when planning pregnancy should stop the drug and appoint other antihypertensive agents permitted for use during pregnancy. If pregnancy occurs, you should immediately cancel the use of the drug Prestans and, if necessary, appoint another therapy.

It is known that the effect of ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to a violation of its development (decrease in renal function, oligohydromnion, slowing the ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If the patient received ACE inhibitors in the II or III trimester of pregnancy, it is recommended to conduct ultrasound of the fetus to assess the condition of the skull and kidney function.

Neonates whose mothers received ACE inhibitors during pregnancy, need careful medical supervision because of risk of hypotension, oliguria and hyperkalemia (see "Contraindications" and "Special instructions").

The limited data available on amlodipine and other BCC in pregnancy indicate that the drug does not have a negative impact on the fetus. However, there is a risk of lengthening the birth.

Lactation

It is not recommended to take Prestans during lactation due to the lack of appropriate clinical experience of perindopril and amlodipine both in the form of monotherapy and in combination.

If necessary, taking the drug should stop breastfeeding.

Side effect:

The frequency of adverse reactions, which were noted during monotherapy with perindopril and amlodipine, is given in the form of the following gradation: very often (&ge1/10) often (&ge1/100, <1/10) infrequently (&ge1/1000, <1/100) rarely (&ge1/10000, <1/1000) very rarely (<1/10000), including individual messages of unspecified frequency (the frequency can not be calculated from available data).

The blood, the hematopoietic and lymphatic system: very rarely — leukopenia/neutropenia, agranulocytosis, pancytopenia, thrombocytopenia, haemolytic anaemia in patients with congenital deficit glukozo-6-fosfatdegidrogenaza, decrease in hemoglobin concentration and hematocrit.

From the immune system: infrequently-urticaria.

Metabolic disorders: uncommon — increased body mass, decrease in body weight very rarely — hyperglycemia.

From the Central nervous system: often-drowsiness, dizziness, headache, paresthesia infrequently — insomnia, mood lability, sleep disturbance, tremor, hypesthesia is very rare — peripheral neuropathy, confusion.

On the part of the organ of vision: often-visual impairment.

On the part of the organ of hearing: often noise in the ears.

From the CCC: often-heartbeat, blood flow to the skin, a marked decrease in blood PRESSURE is infrequent-fainting rarely-chest pain is very rare-angina, myocardial infarction, possibly due to excessive decrease in blood PRESSURE in patients at high risk (see "Special instructions"), arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), stroke, possibly due to excessive decrease in blood PRESSURE in patients at high risk (see" special instructions"), vasculitis.

From the respiratory system: often — shortness of breath, cough infrequently — rhinitis, bronchospasm very rarely-eosinophilic pneumonia.

On the part of the digestive system: often-abdominal pain, nausea, vomiting, dyspepsia, impaired taste perception, diarrhea, constipation infrequently — dryness of the oral mucosa is very rare — pancreatitis, hyperplasia of gums, gastritis.

The liver and biliary tract: very rarely — hepatitis, cholestatic jaundice, cytolytic or cholestatic hepatitis (see "Special instructions").

On the part of the skin and subcutaneous fat: often-skin itching, rash infrequently — angioedema of the face, limbs, lips, mucous membranes, tongue, glottis and/or larynx (see "Special instructions"), alopecia, hemorrhagic rash, photosensitization, increased sweating is very rare — angioedema, multiform erythema, Stevens-Johnson syndrome.

From the musculoskeletal system and connective tissue: often — muscle spasms infrequently — arthralgia, myalgia, back pain.

On the part of the kidneys and urinary tract: infrequently — urinary disorders, nicturia, frequent urination, renal failure is very rare — severe renal failure.

On the part of the reproductive system and breast: infrequently — impotence, gynecomastia.

Common disorders and symptoms: often — peripheral edema, asthenia, increased fatigue infrequently — chest pain, malaise.

Laboratory parameters: rare — increased levels of bilirubin rarely — increased activity of hepatic enzymes: AST, ALT (most often combined with cholestasis) unspecified frequency — increasing the concentration of urea and creatinine in blood serum, hyperkalemia (see "Special instructions").

Drug interaction:

Perindopril

1. Deprecated combinations of drugs

Potassium-sparing diuretics, potassium preparations and potassium-containing salt substitutes: ACE inhibitors reduce the loss of potassium by the kidneys caused by the diuretic. Potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium preparations and potassium-containing salt substitutes can lead to a significant increase in serum potassium (see Special instructions). If you need a joint use of an ACE inhibitor and the above means (in the case of confirmed hypokalemia), caution should be exercised and regular monitoring of potassium in the blood plasma and ECG parameters.

Lithium preparations: with the simultaneous use of lithium preparations and ACE inhibitors, a reversible increase in the lithium content in the blood plasma and associated toxic effects may occur. Simultaneous use of perindopril and lithium drugs is not recommended. If necessary, such therapy requires regular monitoring of the lithium content in the blood plasma (see "Special instructions").

Estramustine: combined use is accompanied by an increased risk of angioedema.

2. A combination of drugs that requires special attention

NSAIDs, including high doses of acetylsalicylic acid (more than 3 g/day): NSAIDs administration can reduce the diuretic, natriuretic and hypotensive effects. With significant loss of fluid, as well as in elderly patients, acute renal failure may develop (due to a decrease in the speed of glomerular filtration). Patients need to compensate for the loss of fluid and at the beginning of treatment to carefully monitor the function of the kidneys.

Hypoglycemic agents (insulin, sulfonylurea derivatives): ACE inhibitors can enhance the hypoglycemic effect of insulin and sulfonylurea derivatives in patients with diabetes mellitus. The development of hypoglycemia is very rare (probably due to increased glucose tolerance and reduced insulin requirements).

3. A combination of drugs that requires attention

Diuretics (thiazide and loop): in patients receiving diuretics, especially with excessive removal of fluid and/or electrolytes, at the beginning of therapy with an ACE inhibitor, there may be a significant decrease in blood PRESSURE, the risk of which can be reduced by canceling the diuretic, the introduction of an increased amount of liquid and/or sodium chloride, as well as prescribing perindopril in a low dose with its further gradual increase.

Sympathomimetics: may weaken the hypotensive effect of ACE inhibitors.

Gold drugs: the appointment of ACE inhibitors, including perindopril, patients receiving injectable gold preparations (sodium aurothiomalate) was recorded narutopedia reaction (redness of skin, nausea, vomiting, hypotension).

Allopurinol, cytostatic and immunosuppressive agents, corticosteroids (with systemic use) and procainamide: simultaneous use with ACE inhibitors may be accompanied by an increased risk of leukopenia.

General anaesthetic products: the combined use of ACE inhibitors and General anaesthetic products can lead to increased hypotensive effect.

Amlodipine

1. Deprecated combinations of drugs

Dantrolen (intravenous administration): in laboratory animals, cases of ventricular fibrillation with lethal outcome were observed against the background of verapamil and intravenous dantrolen administration. The combined use of dantrolene and amlodipine should be avoided by extrapolating the available data.

2. A combination of drugs that requires special attention

Cytochrome CYP3A4 inducers (rifampicin, St. John's wort preparations, anticonvulsants, such as carbamazepine, phenobarbital, phenytoin, phosphenitoin, primidone): it is possible to reduce the plasma concentration of amlodipine due to increased metabolism in the liver. Care should be taken while using amlodipine and inducers of microsomal oxidation and, if necessary, adjust the dose of amlodipine.

Cytochrome CYP3A4 inhibitors (Itraconazole, ketoconazole): may increase plasma concentrations of amlodipine and increase the risk of side effects. Care should be taken while using amlodipine and Itraconazole or ketoconazole, if necessary, adjust the dose of amlodipine.

3. A combination of drugs that requires attention

Beta-blockers used in chronic heart failure (bisoprolol, carvedilol, metoprolol): the risk of hypotension and deterioration of chronic heart failure in patients with uncontrolled or latent chronic heart failure (increased negative inotropic effect). Also beta-blockers can reduce excessive reflex cardiac sympathetic activation against the background of concomitant chronic heart failure.

Other combinations of drugs

Noted the use safety of amlodipine when used together in combination with tiazidnami dioretikami, beta-adrenoblokatorami, ACE inhibitors, nitrates in prolonged dosage forms nitroglycerin (sublingual use), digoxin, warfarin, atorvastatin, sildenafilum, antacids (algeldrat, magnesium hydroxide), simethicone, cimetidine, NSAIDs, antibiotics and hypoglycemic agents for oral administration.

In addition, in special studies showed no interaction of the following drugs and products with amlodipine:

• the combined use of amlodipine and cimetidine pharmacokinetic parameters of amlodipine have not changed
  
• in the joint application of amlodipine and sildenafil, there was no increase in the hypotensive effect of each of the drugs
  
• grapefruit juice: in a study involving 20 healthy volunteers, it was shown that taking 240 ml of grapefruit juice together with a single dose of amlodipine (10 mg orally) did not have a significant effect on the pharmacokinetics of amlodipine.
  

Amlodipine does not affect the pharmacokinetics of the following drugs:

• atorvastatin: receiving repeated doses of amlodipine 10 mg in combination with atorvastatin in a dose of 80 mg does not lead to a significant change in the equilibrium pharmacokinetic parameters of atorvastatin
  
• digoxin: co-administration of amlodipine and digoxin is not accompanied by changes in serum digoxin and renal clearance of digoxin in healthy volunteers
  
• warfarin: in healthy male volunteers who received warfarin, the addition of amlodipine did not have a significant effect on the change in the value of prothrombin time due to warfarin
  
• cyclosporine: amlodipine does not significantly affect the pharmacokinetic parameters of cyclosporine.
  

1. A combination of drugs that requires special attention:

Baclofen: hypotensive effect may be enhanced. It is necessary to control blood PRESSURE and kidney function, if necessary — to adjust the dose of amlodipine.

2. The combination of meds that require attention:

Hypotensive agents (eg beta-blockers) and vasodilators: may increase the hypotensive effect of perindopril and amlodipine. Caution should be exercised while prescribing with nitroglycerin, other nitrates or other vasodilators, since it is possible an additional reduction in blood PRESSURE.

Corticosteroids (mineralocorticosteroids and GCS), tetracosactide: reduction of hypotensive action (retention of liquid and sodium ions as a result of corticosteroids).

Alpha-blockers (prazosin, alfusosin, doxazosin, tamsulosin, terazosin): increased hypotensive action and increased risk of orthostatic hypotension.

Amifostine: may increase hypotensive action of amlodipine.

Tricyclic antidepressants / neuroleptics / General anaesthetics: increased hypotensive effect and increased risk of orthostatic hypotension.

Dosage and administration:

Inside, 1 table. 1 time a day, preferably in the morning, before meals.

The dose of the drug Prestans is selected after previously conducted dose titration of the individual components of the preparation of perindopril and amlodipine is patients with arterial hypertension and stable angina.

If necessary, the therapeutic dose of the drug Prestans can be changed on the basis of individual selection of doses of individual components:

5 mg of perindopril + amlodipine 5 mg or 5 mg of perindopril + amlodipine 10 mg, or 10 mg of perindopril + amlodipine 5 mg, or 10 mg of perindopril + amlodipine 10 mg.

Prestans in doses of 10 mg perindopril + 10 mg amlodipine is the maximum daily dose of the drug, which is not recommended to exceed.

Elderly patients and patients with renal insufficiency (see "Pharmacokinetics" and " Specific instructions»)

The excretion of perindoprilat in elderly patients and patients with renal insufficiency is slowed. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma.

Prestance may be prescribed to patients with creatinine Cl equal to or greater than 60 ml / min.

Prestans is contraindicated in patients with creatinine Cl <60 ml/min in Such patients it is recommended that the selection of individual doses of perindopril and amlodipine. The change in the concentration of amlodipine in blood plasma is not correlated with the degree of severity of renal failure.

Patients with hepatic insufficiency (see "Method of application and dosage" and "Special instructions»)

Caution should be exercised when prescribing the drug to patients with Prestans liver failure due to the lack of recommendations for dosing the drug in such patients.

Children and adolescents

Prestans should not be administered to children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of the use of perindopril and amlodipine in these groups of patients both in the form of monotherapy and in the form of combination therapy.

Overdose:

There is no information about the overdose of the drug Prestans.

Amlodipine

Information on overdose of amlodipine is limited.

Symptoms: a marked decrease in blood pressure WITH the possible development of reflex tachycardia and excessive peripheral vasodilation (risk of severe and persistent hypotension, including the development of shock and death).

Treatment: gastric lavage, the appointment of activated carbon (especially in the first 2 h after the overdose), the maintenance functions of the cardiovascular system, exalted position of extremities, control and BCC diureza, symptomatic and supportive therapy, in/with the introduction of calcium gluconate and dopamine. Dialysis is ineffective. With a significant decrease in blood PRESSURE should be monitored in a patient in the cardiology intensive care unit. In the absence of contraindications to restore vascular tone and blood PRESSURE, you can use vasoconstrictors.

Perindopril

Data on perindopril overdose are limited.

Symptoms: significant decrease in blood PRESSURE, shock, electrolyte disorders, renal failure, hyperventilation, tachycardia, heartbeat, bradycardia, dizziness, anxiety and cough.

Treatment: with a significant decrease in blood PRESSURE, the patient should be transferred to a supine position with raised legs, if necessary, correction of hypovolemia (for example, in/in infusion of 0, 9% sodium chloride solution). It is also possible to/in the introduction of angiotensin II and/or catecholamines. With hemodialysis, you can remove perindopril from the systemic circulation (see "Special instructions"). In bradycardia resistant to therapy, it may be necessary to install an artificial pacemaker. Dynamic control of physical state, creatinine concentration and blood plasma electrolytes is necessary.

Emergency measures are reduced to the removal of the drug from the body: gastric lavage and/or the appointment of activated carbon, followed by the restoration of water-electrolyte balance.

Special instruction:

Special instructions relating to perindopril and amlodipine are applicable to the drug Prestans.

Perindopril

Hypersensitivity/angioedema

When taking ACE inhibitors, including perindopril, in rare cases, there may be the development of angioedema of the face, limbs, lips, mucous membranes, tongue, voice slit and/or larynx (see "Side effects"). When symptoms appear, the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling affects only the face and lips, its manifestations usually take place independently, although antihistamines may be used to treat the symptoms.

Angioedema, accompanied by edema of the larynx, can lead to death. Swelling of the tongue, glottis or larynx may cause airway obstruction. When such symptoms appear, epinephrine (adrenaline) should be administered subcutaneously and/or respiratory tract patency should be ensured. The patient should be under medical supervision until complete and permanent disappearance of symptoms.

In patients with angioedema in history, not associated with the use of ACE inhibitors, the risk of its development may be increased when taking drugs of this group (see "Contraindications").

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops. In this case, patients have abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases, without prior angioedema of the face and with normal C1-esterase. The diagnosis is established by computed tomography of the abdominal region